Urge urinary incontinence (UUI) remains a common and often debilitating condition for women in the US and other industrialized nations. UUI is generally caused by detrusor instability (DI) and is currently managed primarily with oral anticholinergic medications. However, these medications are commonly discontinued due to significant side effects or lack of efficacy and there remains a sizeable population of women who continue to suffer from severe urge urinary incontinence. A pilot study recently performed at this institution in subjects with severe UUI showed that 150U of botulinum-A toxin (Botox) injected into the detrusor muscle of the bladder will dramatically reduce urinary leakage for at least 3 months without any significant adverse effects. Recent studies have reported that 300 Units of Botox injected into subjects with detrusor hyperreflexia (a condition similar to DI) will also dramatically reduce urinary incontinence. We postulate that higher doses of Botox injected into women with DI will also substantially reduce these patients' urinary leakage without causing significant urinary retention or other adverse events. We propose a randomized, placebo controlled trial of 200 and 300Units of Botox in a cohort of subjects with severe UUI. After obtaining baseline measurements of incontinence including questionnaires, bladder diaries, 24-hour pad weight measurements and urodynamic testing, we will cystoscopically inject the detrusor with either placebo or Botox. Subjects will be evaluated regularly for 9 months after the injection using the same instruments to measure outcomes. We expect to see considerable, though temporary, improvement of urinary leakage without significant urinary retention. This study should provide valuable information concerning the efficacy of Botox for severe UUI, the duration of clinical effects of Botox, voiding function after reinnervation and incidence of significant side effects. It will provide valuable data to allow for further studies on the clinical and cost-effectiveness of Botox for detrusor instability and urge urinary incontinence.